Arylamino pyrimidinic derivatives

ABSTRACT

Compounds of the formula ##SPC1## 
     Wherein Ar is phenyl or phenyl substituted by one or more halogens, by a trifluoromethyl or a methylenedioxy, by one or more methoxy, by an alkyl having one to 4 carbon atoms or by a dimethylamino, 
     And R is ##EQU1## or --O-- ##EQU2## or ##EQU3## wherein R 1  and R 2  each are hydrogen or alkyl of 1 to 4 carbon atoms, or ##EQU4## is pyrrolidino, morpholino, piperidino or piperazino N&#39;-substituted by alkyl of 1 to 4 carbon atoms, or phenyl; R 3  and R 4  each are alkyl of 1 to 3 carbon atoms or ##EQU5## is morpholino, pyrrolidino, piperidino or hexamethyleneimino, n is an integer of 1 to 5; and R 5  is alkyl of 1 to 4 carbon atoms, 2,3-dihydroxypropyl or 2,2-dimethyl dioxolan-4-yl methyl or hydroxycarbonylmethyl. 
     The compounds are obtained by reacting 2-Ar-2-chloro-6-methyl pyrimidine, with ##SPC2## 
     The compounds possess sedative, antiinflammatory, antiulcerous, vasodilatatory, antibronchoconstrictive, anticholinergic, diuretic, spasmolytic, cardiac analeptic, analgesic and myorelaxant properties.

The present invention relates to novel arylamino pyrimidinic derivatives, their process of preparation and their therapeutic application.

The novel derivatives according to the invention correspond to the general formula: ##SPC3##

In which:

Ar represents an unsubstituted phenyl ring or a phenyl ring substituted by one or more halogen atoms, by a trifluoromethyl or a methylene dioxy group, by one or more methoxy groups, by an alkyl radical containing up to 4 carbon atoms or by a dimethylamino group; and

R represents: a carboxamidic group of formula: ##EQU6## in which R₁ and R₂ each represent a hydrogen atom or an alkyl radical containing up to 4 carbon atoms, or form together with the nitrogen atom to which they are attached a heterocyclic ring selected from the following: pyrrolidino, morpholino, piperidino or piperazino N'-substituted by an alkyl radical containing up to 4 carbon atoms or by a phenyl ring, or an amino alkoxy chain of formula: ##EQU7## in which R₃ and R₄ each represent an alkyl radical containing 1 to 3 carbon atoms, or may form togerher with the nitrogen atom to which they are attached, a heterocyclic ring selected from the following: morpholino, pyrrolidino, piperidino and hexamethyleneimino, n being an integer of from 1 to 5, or an alkoxycarbonyl group of formula ##EQU8## in which R₅ represents an alkyl radical containing up to 4 carbon atoms, a 2,3-dihydroxypropyl radical or a 2,2-dimethyl dioxolan -4-yl methyl radical, or a hydroxycarbonylmethyl radical.

The process according to the invention consists in condensing in acetic acid and in the presence of hydrochloric acid, a 2-aryl-4-chloro-6-methyl pyrimidine of the general formula: ##SPC4##

in which:

Ar represents an unsubstituted phenyl ring or a phenyl ring substituted by one or more halogen atoms, by a trifluoromethyl or a methylene dioxy group, by one or more methoxy groups, by an alkyl radical containing up to 4 carbon atoms or by a dimethylamino group, with an anilino derivative of the general formula: ##SPC5##

in which R' represents: a carboxamidic group of formula ##EQU9## in which: R₁ and R₂ each represent a hydrogen atom or an alkyl radical containing up to 4 carbon atoms, or form together with the nitrogen atom to which they are attached, a heterocyclic ring selected from the following: pyrrolidino, morpholino, piperidino or piperazino N'-substituted by an alkyl radical containing up to 4 carbon atoms or by a phenyl ring, or an amino alkoxy chain of formula ##EQU10## in which R₃ and R₄ each represent an alkyl radical containing 1 to 3 carbon atoms, or may form, together with the nitrogen atom to which they are attached, a heterocyclic ring selected from the following: morpholino, pyrrolidino, piperidino and hexamethyleneimino, n being an integer of from 1 to 5, or an alkoxycarbonyl group of formula ##EQU11## in which R₅ represents an alkyl radical containing up to 4 carbon atoms, or a hydroxycarbonylmethyl radical, to produce a derivative corresponding to the general formula: ##SPC6##

and, on occasion, to subject a derivative of formula I', in which R' represents a methoxycarbonyl group, to a transesterification process in the presence of sodium with 2,2-dimethyl-4' hydroxymethyl-1,3-dioxolane to produce a derivative of formula: ##SPC7##

which may then be transformed into a derivative of formula: ##SPC8##

by opening of the dioxolane ring by the action of 2N hydrochloric acid.

The following preparations are given by way of example to illustrate the invention.

EXAMPLE 1 2-(3',4',5'- trimethoxy phenyl)-4-(para pyrrolidino carbonyl phenylamino) -6-methyl pyrimidino

(Code No. 72271)

A mixture of 44.2g of 2-(3',4',5'-trimethoxy phenyl)-4-chloro-6-methyl pyrimidine and 28.6 g of 4 - pyrrolidino carbonyl anilino in 300 c.c. of acetic acid in the presence of 0.45 cc of concentrated hydrochloric acid is heated at 80°C for 40 minutes. After cooling, the solution is diluted with 2.5 l of water and alkalinised with ammonia.

The precipitate formed is filtered, washed with water and recrystallized from ethyl acetate.

Melting point = 210°C Yield = 71%

Empirical formula = C₂₅ H₂₈ N₄ O₄

Elementary analysis:

    ______________________________________                                                 C         H          N                                                 ______________________________________                                         Calculated %                                                                             66.94       6.29       12.49                                         Found %   66.85       6.40       12.49                                         ______________________________________                                    

EXAMPLE 2 2 - (3' - trifluoromethylphenyl)-4- [ortho (β, γ-dihydroxy propoxycarbonyl) phenyl amino] -6-methyl pyrimidine. (Code No: 72 502)

1st stage N - [2-(3'-trifluoromethylphenyl)- 6-methyl-4-pyrimidyl]methyl anthranilate.

(Code No: 72 437)

This derivative is obtained by the mode of operation described in Example 1 the recrystallisation being carried out in isopropyl alcohol and not ethyl acetate.

Melting point = 111°C Yield = 86%

Empirical formula = C₂₀ H₁₆ F₃ N₃ O₂

Elementary analysis:

    ______________________________________                                                 C         H          N                                                 ______________________________________                                         Calculated %                                                                             62.01       4.16       10.85                                         Found %   62.06       4.21       10.76                                         ______________________________________                                    

2nd stage N-[2-(3'trifluoromethyl phenyl) -6-methyl-4-pyrimidyl](2",2" -dimethyl dioxolan -4"-yl) methyl anthranilate.

(Code No. 72 495)

500 c.c of 2,2 - dimethyl -4-hydroxymethyl dioxolane and then 0.6 g. of sodium are introduced into a reaction vessel which has previously been purged with nitrogen. The vessel is warmed just until total dissolution of the sodium is effected. After returning to ambient temperature, 162 g of N-[2-(3'-trifluoromethyl phenyl)-6-methyl -4-pyrimidyl] methyl anthanilate, of code No. 72 437 obtained in the preceding stage, is introduced into the reaction vessel. The mixture is heated for 5 hours at 145°C, under nitrogen, the methanol formed during the course of the reaction being distilled off. After cooling, the solution obtained is diluted with 3 liters of water. The precipitate formed is filtered, washed with water and recrystallised from ethanol.

Melting point = 107°C Yield = 80%

Empirical formula = C₂₅ H₂₄ F₃ N₃ O₄

Molecular weight = 487.46

Elementary analysis:

    ______________________________________                                                 C         H          N                                                 ______________________________________                                         Calculated %                                                                             61.59       4.96       8.62                                          Found %   61.64       5.04       8.77                                          ______________________________________                                    

3rd stage 2-(3'-trifluoromethyl phenyl)-4- ortho (ξ,γ-dihydroxy propoxycarbonyl) phenylamino]-6-methyl pyrimidine

(Code No. 72 502)

A suspension of 111.8g of N-[2-(3'-trifluoromethylphenyl)-6-methyl-4-pyrimidyl] (2",2"-dimethyl dioxolan-4"-yl) methyl anthranilate of code No. 72 495 obtained in the preceding stage, in 750 c.c of 2N hydrochloric acid is heated for 20 minutes under reflux.

After cooling, the precipitate obtained is filtered, washed with water, dissolved in 1 l of 50% alcohol and neutralised with triethylamine. The solution is concentrated the residue is taken up in 1 l of water, the precipitate is filtered, washed with water and recrystallised from ethanol

Melting point = 154°C Yield = 74%

Empirical formula = C₂₂ H₂₀ F₃ N₃ O₄

Elementary analysis:

    ______________________________________                                                 C         H          N                                                 ______________________________________                                         Calculated %                                                                             59.06       4.51       9.39                                          Found %   59.10       4.64       9.51                                          ______________________________________                                    

The derivatives listed in the following Table I have been prepared by the same mode of operation.

                                      TABLE I                                      __________________________________________________________________________                                             Melt-                                                                          ing                                    Code                      Empirical Molecular                                                                          point                                                                             Yield                                                                             Elementary analysis              No. Ar                    formula   weight                                                                             (°C)                                                                       (%)      C   H  N                   __________________________________________________________________________                                                   Calculated                       72 327                    C.sub.20 H.sub.19 ClN.sub.4 O                                                            366.84                                                                             232                                                                               30 %     65.48                                                                              5.22                                                                              15.27                                                             Found (%)                                                                            65.36                                                                              5.17                                                                              15.18                                                             Calculated                       72 255                                                                             "                     C.sub.22 H.sub.21 ClN.sub.4 O                                                            392.88                                                                             242                                                                               50 (%)   67.25                                                                              5.39                                                                              14.24                                                             Found (%)                                                                            67.10                                                                              5.25                                                                              14.10                                                             Calculated                       72 256                                                                             "                     C.sub.22 H.sub.21 ClN.sub.4 O.sub.2                                                      408.38                                                                             220                                                                               50 (%)   64.62                                                                              5.18                                                                              13.70                                                             Found (%)                                                                            64.51                                                                              4.98                                                                              13.51                                                             Calculated                       72 276                                                                             "                     C.sub.23 H.sub.23 ClN.sub.4 O                                                            406.90                                                                             238                                                                               38 (%)   67.89                                                                              5.70                                                                              13.77                                                             Found (%)                                                                            67.89                                                                              5.90                                                                              13.61                                                             Calculated                       72 292                                                                             "                     C.sub.23 H.sub.24 ClN.sub.5 O                                                            421.92                                                                             215                                                                               27 (%)   65.47                                                                              5.73                                                                              16.60                                                             Found (%)                                                                            65.35                                                                              5.58                                                                              16.67                                                             Calculated                       72 260                                                                             "                     C.sub.28 H.sub.26 ClN.sub.5 O                                                            479.99                                                                             230                                                                               54 (%)   69.48                                                                              5.42                                                                              14.47                                                             Found %                                                                              69.40                                                                              5.25                                                                              14.27                                                             Calculated                       72 257                    C.sub.18 H.sub.15 ClN.sub.4 O                                                            338.79                                                                             234                                                                               68 %     63.81                                                                              4.46                                                                              16.54                                                             Found (%)                                                                            63.96                                                                              4.53                                                                              16.35                                                             Calculated                       72 311                                                                             "                     C.sub.18 H.sub.15 ClN.sub.4 O                                                            338.79                                                                             228                                                                               58 (%)   63.81                                                                              4.46                                                                              16.54                                                             Found (%)                                                                            63.65                                                                              4.56                                                                              16.51                                                             Calculated                       72 283                                                                             "                     C.sub.20 H.sub.18 ClN.sub.3 O.sub.2                                                      367.82                                                                             180                                                                               84 (%)   65.30                                                                              4.93                                                                              11.42                                                             Found (%)                                                                            65.50                                                                              5.13                                                                              11.22                                                             Calculated                       71 442                                                                             "                     C.sub.19 H.sub.16 ClN.sub.3 O.sub.2                                                      353.79                                                                             150                                                                               40 (%)   64.50                                                                              4.56                                                                              11.88                                                             Found (%)                                                                            64.30                                                                              4.38                                                                              11.91                                                             Calculated                       71 488                                                                             "                     C.sub.24 H.sub.24 ClN.sub.3 O.sub.4                                                      453.91                                                                             139                                                                               50 (%)   63.50                                                                              5.33                                                                              9.26                                                              Found (%)                                                                            63.60                                                                              5.42                                                                              9.15                                                              Calculated                       71 530                                                                             "                     C.sub.21 H.sub.20 ClN.sub.3 O.sub.4                                                      413.85                                                                             173                                                                               50 (%)   60.94                                                                              4.87                                                                              10.15                                                             Found (%)                                                                            60.84                                                                              4.94                                                                              10.26                                                             Calculated                       72 755                    C.sub.22 H.sub.21 FN.sub.4 O                                                             376.42                                                                             246                                                                               33 (%)   70.19                                                                              5.62                                                                              14.89                                                             Found (%)                                                                            70.16                                                                              5.56                                                                              14.95                                                             Calculated                       72 754                    C.sub.22 H.sub.21 FN.sub.4 O.sub.2                                                       392.42                                                                             187                                                                               71 (%)   67.33                                                                              5.39                                                                              14.28                                                             Found (%)                                                                            67.53                                                                              5.33                                                                              14.38                                                             Calculated                       72 741                                                                             "                     C.sub.23 H.sub.23 FN.sub.4 O                                                             390.45                                                                             214                                                                               66 (%)   70.75                                                                              5.94                                                                              14.35                                                             Found (%)                                                                            70.55                                                                              5.90                                                                              14.38                                                             Calculated                       72 783                                                                             "                     C.sub.18 H.sub.15 FN.sub.4 O                                                             322,33                                                                             224                                                                               72 (%)   67.07                                                                              4.69                                                                              17.38                                                             Found (%)                                                                            66.87                                                                              4.87                                                                              17.28                                                             Calculated                       72 773                                                                             "                     C.sub.18 H.sub.15 FN.sub.4 O                                                             322.33                                                                             219                                                                               55 (%)   67.07                                                                              4.69                                                                              17.38                                                             Found (%)                                                                            67.17                                                                              4.66                                                                              17.45                                                             Calculated                       72 778                                                                             "                     C.sub.20 H.sub.18 FN.sub.3 O.sub.2                                                       351.38                                                                             168                                                                               82 (%)   68.36                                                                              5.16                                                                              11.96                                                             Found (%)                                                                            68.37                                                                              5.13                                                                              12.06                                                             Calculated                       72 772                                                                             "                     C.sub.19 H.sub.16 FN.sub.3 O.sub.2                                                       337.34                                                                             119                                                                               88 (%)   67.64                                                                              4.80                                                                              12.46                                                             Found (%)                                                                            67.80                                                                              4.79                                                                              12.30                                                             Calculated                       72 796                                                                             "                     C.sub.24 H.sub.24 FN.sub.3 O.sub.4                                                       437.46                                                                             105                                                                               63 (%)   65.89                                                                              5.53                                                                              9.61                                                              Found (%)                                                                            65.86                                                                              5.42                                                                              9.59                                                              Calculated                       72 826                    C.sub.21 H.sub.20 FN.sub.3 O.sub.4                                                       397.39                                                                             143                                                                               31 (%)   63.47                                                                              5.07                                                                              10.57                                                             Found (%)                                                                            63.43                                                                              5.01                                                                              10.73               730234                                                                             "                     C.sub.19 H.sub.16 FN.sub.3 O.sub.2 +1/2H.sub.2                                 O         346.35                                                                             179                                                                               50 (%)   65.88                                                                              4.95                                                                              12.13                                                             Found (%)                                                                            66.03                                                                              4.76                                                                              12.02                                                             Calculated                       72 473                    C.sub.23 H.sub.21 F.sub.3 N.sub.4 O                                                      426.43                                                                             206                                                                               55 (%)   64.78                                                                              4.96                                                                              13.14                                                             Found (%)                                                                            64.74                                                                              4.76                                                                              13.21                                                             Calculated                       72 420                                                                             "                     C.sub.23 H.sub.21 F.sub.3 N.sub.4 O.sub.2                                                442.43                                                                             193                                                                               65 (%)   62.44                                                                              4.78                                                                              12.66                                                             Found (%)                                                                            62.26                                                                              4.80                                                                              12.50                                                             Calculated                       72 421                                                                             "                     C.sub.24 H.sub.23 F.sub.3 N.sub.4 O                                                      440.46                                                                             204                                                                               51 (%)   65.44                                                                              5.26                                                                              12.72                                                             Found (%)                                                                            65.33                                                                              5.29                                                                              12.72                                                             Calculated                       72 503                                                                             "                     C.sub.29 H.sub.26 F.sub.3 N.sub.5 O                                                      517.54                                                                             198                                                                               27 (%)   67.30                                                                              5.06                                                                              13.51                                                             Found (%)                                                                            67.29                                                                              5.26                                                                              13.33                                                             Calculated                       72 419                                                                             "                     C.sub.19 H.sub.15 F.sub.3 N.sub.4 O                                                      372.34                                                                             193                                                                               81 (%)   61.29                                                                              4.06                                                                              15.05                                                             Found (%)                                                                            61.20                                                                              4.20                                                                              15.03                                                             Calculated                       72 432                                                                             "                     C.sub.19 H.sub.15 F.sub.3 N.sub.4 O                                                      372.34                                                                             180                                                                               83 (%)   61.29                                                                              4.06                                                                              15.05                                                             Found (%)                                                                            61.46                                                                              3.88                                                                              14.83                                                             Calculated                       72 505                    C.sub.21 H.sub.18 F.sub.3 N.sub.3 O.sub.2                                                401.38                                                                             260                                                                               71 (%)   62.84                                                                              4.58                                                                              10.47                                                             Found (%)                                                                            62.87                                                                              4.67                                                                              10.56                                                             Calculated                       72 623                    C.sub.23 H.sub.22 N.sub.4 O.sub.3                                                        402.44                                                                             225                                                                               69 (%)   68.64                                                                              5.51                                                                              13.92                                                             Found (%)                                                                            68.46                                                                              5.60                                                                              13.78                                                             Calculated                       72 621                                                                             "                     C.sub.23 H.sub.22 N.sub.4 O.sub.4                                                        418.44                                                                             260                                                                               31 (%)   66.01                                                                              5.30                                                                              13.39                                                             Found (%)                                                                            65.97                                                                              5.35                                                                              13.22                                                             Calculated                       72 687                                                                             "                     C.sub.24 H.sub.24 N.sub.4 O.sub.3                                                        416.46                                                                             248                                                                               78 (%)   69.21                                                                              5.81                                                                              13.45                                                             Found (%)                                                                            69.30                                                                              5.80                                                                              13.27                                                             Calculated                       72 608                                                                             "                     C.sub.19 H.sub.16 N.sub.4 O.sub.3                                                        348.35                                                                             210                                                                               51 (%)   65.51                                                                              4.63                                                                              16.08                                                             Found (%)                                                                            65.43                                                                              4.69                                                                              16.03                                                             Calculated                       730025                                                                             "                     C.sub.19 H.sub.16 N.sub.4 O.sub.3                                                        348.35                                                                             243                                                                               45 (%)   65.51                                                                              4.63                                                                              16.08                                                             Found (%)                                                                            65.27                                                                              4.70                                                                              16.05                                                             Calculated                       72 613                                                                             "                     C.sub.21 H.sub.19 N.sub.3 O.sub.4                                                        377.39                                                                             180                                                                               83 (%)   66.83                                                                              5.07                                                                              11.14                                                             Found (%)                                                                            66.67                                                                              5.12                                                                              11.33                                                             Calculated                       72 665                                                                             "                     C.sub.20 H.sub.17 N.sub.3 O.sub.4                                                        363.36                                                                             163                                                                               87 (%)   66.11                                                                              4.72                                                                              11.57                                                             Found (%)                                                                            66.05                                                                              4.88                                                                              11.57                                                             Calculated                       72 701                    C.sub.25 H.sub.25 N.sub.3 O.sub.6                                                        463,48                                                                             149                                                                               59 (%)   64,78                                                                              5,44                                                                              9,07                                                              Found (%)                                                                            64.98                                                                              5,36                                                                              9,23                                                              Calculated                       72 686                                                                             "                     C.sub.22 H.sub.21 N.sub.3 O.sub.6                                                        423,41                                                                             161                                                                               73 (%)   62,40                                                                              5,00                                                                              9,93                                                              Found (%)                                                                            62,60                                                                              4,98                                                                              9,92                                                              Calculated                       72 536                    C.sub.25 H.sub.28 N.sub.4 O.sub.5                                                        464,51                                                                             206                                                                               72 (%)   64,64                                                                              608                                                                               12,06                                                             Found (%)                                                                            64,50                                                                              6,15                                                                              11,98                                                             Calculated                       72 317                                                                             "                     C.sub.26 H.sub.30 N.sub.4 O.sub.4                                                        462,53                                                                             217                                                                               59 (%)   67,51                                                                              6,54                                                                              12,11                                                             Found (%)                                                                            67,42                                                                              6,52                                                                              11,91                                                             Calculated                       72 462                                                                             "                     C.sub.26 H.sub.31 N.sub.5 O.sub.4                                                        477,59                                                                             190                                                                               37 (%)   65,39                                                                              6,54                                                                              14,67                                                             Found (%)                                                                            65,38                                                                              6,66                                                                              14,54                                                             Calculated                       72 450                                                                             "                     C.sub.31 H.sub.33 N.sub.5 O.sub.4                                                        539,61                                                                             230                                                                               42 (%)   69,00                                                                              6,16                                                                              12,98                                                             Found (%)                                                                            68,80                                                                              6,24                                                                              12,84                                                             Calculated                       72 442                    C.sub.21 H.sub.22 N.sub.4 O.sub.4                                                        394.42                                                                             190                                                                               54 (%)   63.94                                                                              5.62                                                                              14.21                                                             Found (%)                                                                            63.94                                                                              5.71                                                                              14.11                                                             Calculated                       72 417                                                                             "                     C.sub.21 H.sub.22 N.sub.4 O.sub.4                                                        394.42                                                                             212                                                                               46 (%)   63.94                                                                              5.62                                                                              14.21                                                             Found (%)                                                                            63.74                                                                              5.66                                                                              14.19                                                             Calculated                       72 247                                                                             "                     C.sub.23 H.sub.25 N.sub.3 O.sub.5                                                        423.45                                                                             210                                                                               81 (%)   65.23                                                                              5.95                                                                              9.93                                                              Found (%)                                                                            65.27                                                                              5.98                                                                              9.87                                                              Calculated                       72 479                                                                             "                     C.sub.22 H.sub.23 N.sub.3 O.sub.5                                                        409.43                                                                             121                                                                               52 (%)   64.53                                                                              5.66                                                                              10.26                                                             Found (%)                                                                            64.74                                                                              5.65                                                                              10.31                                                             Calculated                       71 510                                                                             "                     C.sub.27 H.sub.31 N.sub.3 O.sub.7                                                        509.54                                                                             118                                                                               56 (%)   63.64                                                                              6.13                                                                              8.25                                                              Found (%)                                                                            64,84                                                                              6.02                                                                              8.34                __________________________________________________________________________                                              Mel-                                                                       Molec-                                                                             ting                                  Code                          Empirical                                                                             ular                                                                               point                                                                             Yield                                                                             Elementary Analysis             No. Ar                        Formula                                                                               weight                                                                             (°C)                                                                       (%)     C   H  N                   __________________________________________________________________________                                                    Calcu-                          730136                     base                                                                              C.sub.21 H.sub.24 N.sub.4 O                                                           348.43                                                                             155                                                                               94 lated %                                                                             72.38                                                                              6.94                                                                              16.08                                                              Found %                                                                             72.53                                                                              6.86                                                                              16.39                                          hy-                 Calcu-                          730282                     dro                                                                               C.sub.25 H.sub.33 ClN.sub.4 O                                                         441.00                                                                             220                                                                               67 lated %                                                                             68.08                                                                              7.54                                                                              12.71                                          chlo-               Found %                                                                             67.95                                                                              7.74                                                                              12.86                                          ride                                                                                               Calcu-                          730218                     base                                                                              C.sub.23 H.sub.26 N.sub.4 O                                                           374.47                                                                             157                                                                               77 lated %                                                                             73.77                                                                              7.00                                                                              14.96                                                              Found %                                                                             73.88                                                                              7.09                                                                              14.54                                                              Calcu-                          730221                     base                                                                              C.sub.24 H.sub.28 N.sub.4 O                                                           388.50                                                                             130                                                                               51 lated %                                                                             74.19                                                                              7.26                                                                              14.42                                                              Found %                                                                             74.39                                                                              7.36                                                                              14.22                                                              Calcu-                          730591                     base                                                                              C.sub.24 H.sub.30 N.sub.4 O.sub.4                                                     438.51                                                                             133                                                                               62 lated %                                                                             65.73                                                                              6.90                                                                              12.78                                                              Found %                                                                             65.53                                                                              6.95                                                                              12.76                                                              Calcu-                          730229                     base                                                                              C.sub.23 H.sub.26 N.sub.4 O.sub.2                                                     390.47                                                                             121                                                                               57 lated %                                                                             70.74                                                                              6.71                                                                              14.35                                                              Found %                                                                             70.93                                                                              6.88                                                                              14.15                                          hy-                 Calcu-                          730389                     dro-                                                                              C.sub.25 H.sub.31 ClN.sub.4 O                                                         438.99                                                                             177                                                                               41 lated %                                                                             68.40                                                                              7.12                                                                              12.76                                          chlo-               Found %                                                                             68.25                                                                              6.92                                                                              12.79                                          ride                                                                                               Calcu-                          730225                     base                                                                              C.sub.21 H.sub.23 ClN.sub.                                                            382.88                                                                             129                                                                               53 lated %                                                                             65.87                                                                              6.06                                                                              14.63                                                              Found %                                                                             66.07                                                                              6.26                                                                              14.64                                                              Calcu-                          730241                     base                                                                              C.sub.22 H.sub.23 F.sub.3 N.sub.4 O                                                   416.44                                                                             132                                                                               48 lated %                                                                             63.44                                                                              5.57                                                                              13.46                                                              Found %                                                                             63.58                                                                              5.68                                                                              13.56                                                              Calcu-                          730243                     base                                                                              C.sub.24 H.sub.25 F.sub.3 N.sub.4 O                                                   442.47                                                                             133                                                                               75 lated %                                                                             65.14                                                                              5.70                                                                              12.66                                                              Found %                                                                             65.33                                                                              5.70                                                                              12.85                                                              Calcu-                          730224                     base                                                                              C.sub.21 H.sub.23 FN.sub.4 O                                                          366.43                                                                             167                                                                               55 lated %                                                                             68.63                                                                              6.33                                                                              15.29                                                              Found %                                                                             68.94                                                                              6.53                                                                              15.37                                                              Calcu-                          730231                     base                                                                              C.sub.24 H.sub.27 FN.sub.4 O                                                          406.49                                                                             140                                                                               68 lated %                                                                             70.91                                                                              6.70                                                                              13.73                                                              Found %                                                                             71.09                                                                              6.86                                                                              13.66                                                              Calcu-                          730262                     base                                                                              C.sub.21 H.sub.23 ClN.sub.                                                            382,89                                                                             136                                                                               50 lated %                                                                             65,87                                                                              6.06                                                                              14.63                                                              Found %                                                                             66.04                                                                              6.26                                                                              14.58                                                              Calcu-                          730283                     base                                                                              C.sub.25 H.sub.29 ClN.sub.                                                            436,97                                                                             126                                                                               30 lated %                                                                             68.71                                                                              6.69                                                                              12.82                                                              Found %                                                                             68.78                                                                              6.91                                                                              12.98                                                              Calcu-                          730633                     base                                                                              C.sub.26 H.sub.32 N.sub.4 O.sub.5                                                     480.55                                                                             129                                                                               67 lated %                                                                             64.98                                                                              6.71                                                                              11.66                                                              Found %                                                                             64.77                                                                              7.28                                                                              11.60                                          semi-               Calcu-                          730741                     hy-                                                                               C.sub.24 H.sub.30 N.sub.4 O.sub.4                                                     447.52                                                                             111                                                                               34 lated %                                                                             64.41                                                                              6.98                                                                              12.52                                          drate                                                                             + 1/2 H.sub.2 O  Found %                                                                             64.88                                                                              7.00                                                                              12.58                                                              Calcu-                          730732                     base                                                                              C.sub.23 H.sub.25 ClN.sub.                                                            424.92b.2                                                                          134                                                                               73 lated %                                                                             65.01                                                                              5.93                                                                              13.19                                                              Found %                                                                             64.77                                                                              5.90                                                                              13.28                                                              Calcu-                          730695                     "  C.sub.23 H.sub.25 ClN.sub.                                                            424.92b.2                                                                          134                                                                               69 lated %                                                                             65.01                                                                              5.93                                                                              13.19                                                              Found %                                                                             64.78                                                                              6.02                                                                              13.24                                                              Calcu-                          730712                     "  C.sub.24 H.sub.25 F.sub.3 N.sub.4 O.sub.2                                             458.47                                                                             132                                                                               53 lated %                                                                             62.87                                                                              5.50                                                                              12.22                                                              Found %                                                                             62.79                                                                              5.51                                                                              12.40                                                              Calcu-                          730731                     "  C.sub.24 H.sub.26 N.sub.4 O.sub.4                                                     434.48                                                                             112                                                                               72 lated %                                                                             66.34                                                                              6.03                                                                              12.90                                                              Found %                                                                             66.20                                                                              5.93                                                                              12.70                                                              Calcu-                          740 023                    base                                                                              C.sub.23 H.sub.25 FN.sub.4 O.sub.2                                                    408.46                                                                             128                                                                               73 lated %                                                                             67.63                                                                              6.17                                                                              13.72                                                              Found %                                                                             67.86                                                                              6.15                                                                              13.60                                                              Calcu-                          740 108                    base                                                                              C.sub.24 H.sub.28 N.sub.4 O.sub.3                                                     420.50                                                                             150                                                                               67 lated %                                                                             68.55                                                                              6.71                                                                              13.33                                                              Found %                                                                             68.81                                                                              6.91                                                                              13.15                                                              Calcu-                          740 087                    base                                                                              C.sub.24 H.sub.28 N.sub.4 O.sub.2                                                     404.50                                                                             143                                                                               70 lated %                                                                             71.26                                                                              6.98                                                                              13.85                                                              Found %                                                                             71.46                                                                              7.18                                                                              13.68                                                              Calcu-                          740 140                    base                                                                              C.sub.25 H.sub.31 N.sub.5 O.sub.2                                                     433.54                                                                             163                                                                               50 lated %                                                                             69.26                                                                              7.12                                                                              16.16                                                              Found %                                                                             69.16                                                                              7.37                                                                              16.06                                                              Calcu-                          740 067                    base                                                                              C.sub.26 H.sub.32 N.sub.4 O.sub.5                                                     480.55                                                                             142                                                                               77 lated %                                                                             64.98                                                                              6.71                                                                              11.66                                                              Found %                                                                             64.86                                                                              6.91                                                                              11.46                                                              Calcu-                          740391                     base                                                                              C.sub. 23 H.sub.28 N.sub.4 O.sub.3                                                    408.49                                                                             372                                                                               71 lated %                                                                             67.62                                                                              6.91                                                                              13.72                                                              Found %                                                                             67.63                                                                              6.86                                                                              13.71                                                              Calcu-                          740393                     base                                                                              C.sub.23 H.sub.26 N.sub.4 O.sub.2                                                     390.47                                                                             123                                                                               43 lated %                                                                             70.74                                                                              6.71                                                                              14.35                                                              Found %                                                                             70.87                                                                              6.81                                                                              14.33                                                              Calcu-                          740324                     base                                                                              C.sub.24 H.sub.28 N.sub.4 O.sub.2                                                     404.50                                                                             124                                                                               75 lated %                                                                             71.26                                                                              6.98                                                                              13.85                                                              Found %                                                                             71.11                                                                              7.09                                                                              13.78               __________________________________________________________________________

The derivatives of formula I have been tested on animals in the laboratory and have been shown to possess sedative, antiinflammatory, antiulcerous, vasodilatatory, antibronchoconstrictive and anticholinergic, diuretic, spasmolytic, cardiacanaleptic, analgesic and myorelaxant properties, certain of the derivatives possessing hypotensive properties whilst other possess hypertensive properties.

1. Sedative properties

The derivatives of formula I, administered by oral means to the mouse, reduce the number of explorations in the escape enclosure and in an actimeter having luminous beams and photoelectric cells.

By way of example the following Table II lists the percentage diminution in the number of explorations in the escape enclosure, resulting from the administration of 100mg/kg/p.o. of different derivatives of formula I.

                  TABLE II                                                         ______________________________________                                         Code No. of    Percentage diminution of                                        derivatives tested                                                                            number of explorations (%)                                      ______________________________________                                         71 510         40                                                              72 271         40                                                              72 432         35                                                              72 442         60                                                              72 450         35                                                              72 536         75                                                              72 773         45                                                              72 778         35                                                              730 712        32                                                              730 741        30                                                              ______________________________________                                    

Also, the DE 50 of the derivative of code No. 730 229 is 82mg/kg/p.o. for the test on the number of explorations in the escape enclosure and 120mg/kg/p.o. for the test on the number of explorations in the actimeter.

2. Hypertensive properties

Administered by intraveinous means, the derivatives of formula I provoke an increase in the arterial pressure of an anaosthetised rat.

By way of example, the results obtained by the administration of 2 mg/kg/i.v. of different derivatives of formula I are listed in the following Table III.

                  TABLE III                                                        ______________________________________                                         Code Nos. of                                                                               Percentage augmentation                                                                         Duration of                                       derivative tested                                                                          of arterial pressure (%)                                                                        effect (mm)                                       ______________________________________                                         730 712     23               ≃30                                 730 741     27               ≃35                                 ______________________________________                                    

3. Antiulcerous properties

The derivatives of formula I, administered by oral means, reduce the extent of gastric ulcers provoked in a rat by tying of the pylorus (Shay ulcers)

Table IV indicated, by way of example, the results obtained by the administration of 50mg/kg/i.d. of different derivatives of formula I.

                  TABLE IV                                                         ______________________________________                                         Code No. of      Percentage reduction                                          derivative tested                                                                               of shay ulcers %                                              ______________________________________                                         71 510           35                                                            72 255           35                                                            72 257           50                                                            72 260           35                                                            72 276           40                                                            72 311           40                                                            72 317           40                                                            72 417           40                                                            72 432           35                                                            72 502           35                                                            72 613           70                                                            72 621           40                                                            72 687           40                                                            730 225          53                                                            730 231          50                                                            730 283          45                                                            730 282          50                                                            72 754           40                                                            72 773           40                                                            730 025          35                                                            ______________________________________                                    

4. Vasodilatatory properties

The derivatives of formula I are capable of augmenting the flow of the coronary vessels of this isolated heart of a guinea - pig, when said derivatives are added in the perfusion liquid of said organ.

The percentage augmentation of the flow of the isolated heart of the guinea - pig by adding different derivatives of formula I to the perfusion liquid are given by way of example in the following Table V.

                  TABLE V                                                          ______________________________________                                                                   Percentage augment-                                                            ation of flow of                                     Code No. of Dose administered                                                                            isolated heart of                                    derivative tested                                                                          (μg/ml)    guinea - pig (%)                                     ______________________________________                                         72 255      1             45                                                   72 257      1             80                                                   72 260      1             70                                                   72 450      1             85                                                   72 505      1             50                                                   72 613      1             85                                                   72 796      1             60                                                   730283      0.1           61                                                   730241      0.5           77                                                   ______________________________________                                    

5. Antibronchoconstrictive and anticholinergic properties

Injected by intraduodenal means, the derivatives of formula I are capable of opposing the bronchoconstriction provoked in the guinea - pig by the intraveinous injection of acetylcholine and evaluated by the Konzett method.

By way of example, the following Table VI lists the percentage inhibition of the bronchoconstriction following the intraperitoneal injection of 100mg/kg of different derivatives of formula I.

                  TABLE VI                                                         ______________________________________                                         Code No. of    Percentage inhibition                                           derivative tested                                                                             of bronchoconstriction (%)                                      ______________________________________                                         72 255         50                                                              72 276         50                                                              72 311         80                                                              72 502         50                                                              72 608         65                                                              72 826         100                                                             730 025        50                                                              ______________________________________                                    

6. Diuretic properties

The derivatives of formula I, administered by oral means to the mouse, simultaneously with a volume of 1ml of an isotonic solution of sodium chloride per 25g of the corporeal weight of the mouse, are capable of provoking an augmentation of the volume of urine emitted by reference to control animals, the volume being measured for 6 hours following administration.

The following Table VII indicates, by way of example the percentage augmentation of urinary elimination resulting from the administration of 25mg/kg/p.o. of different derivatives of formula I.

                  TABLE VII                                                        ______________________________________                                         Code No. of    Percentage augmentation of                                      derivative tested                                                                             urinary elimination (%)                                         ______________________________________                                         72 292         55                                                              72 327         85                                                              72 417         65                                                              72 419         80                                                              72 432         200                                                             72 495         115                                                             72 623         85                                                              72 701         45                                                              72 754         50                                                              72 773         110                                                             72 783         80                                                              72 826         80                                                              730 025        140                                                             730 229        129                                                             730 695        43                                                              730 712        90                                                              730 731        37                                                              ______________________________________                                    

7. Hypotensive properties

Administered by intraveinous means to an anaesthetised rat, the derivatives of formula I provoke a lowering of the arterial pressure.

By way of example, the following Table VIII mentions the results obtained by administration of different derivatives of formula I.

                  TABLE VIII                                                       ______________________________________                                                   Dose       Percentage reduction                                                                          Duration                                   Code No. of                                                                              administered                                                                              of arterial pressure                                                                          of effect                                  derivative tested                                                                        (mg/kg/i.v.)                                                                              of anaesthetised rate %                                                                       (mn)                                       ______________________________________                                          72 327   1          30             30                                          72 442   1          30             20                                         740 140   1          40             30                                         730 241   2          24             30                                         730 731   1          29             30                                         ______________________________________                                    

8. Cardiac properties

These properties are shown by an augmentation of the force of contractions (positive inotrope action) on the isolated heart of a guinea-pig maintained in a conserving medium and under appropriate experimental conditions.

Also, the derivatives of Code Nos. 72419 and 730218 added to the conserving medium, in a concentration of 1 μg/ml and 0.5 μg/ml, respectively, exert a positive inotrope action on the isolated heart of the guinea-pig. Additionally, the derivative of Code No. 730 712 added to the conserving medium in a concentration of 1 μg/ml, permit an augmentation of 140% in the force of contractions on the isolated heart of the guinea- pig.

9. Analgesic properties

The derivatives of formula I administered by oral means to the mouse, are capable of reducing the number of painful stretchings caused by the intraperitoneal injection of phenylbenzoquinone, acetic acid or bradykinine and can potentialise the analagesic action of dextromoramide in the Eddy test. Administered by oral means to the rat, they protect the animal against crying and jumping in the Randall and Selitto test.

By way of example:

the following table IX shows the results obtained by administration of different derivatives of formula I, these results being estimated by the DE 50 of the derivatives and compared to those following administration of:

amidopyrine or 4-dimethylamino-2,3-dimethyl-1 phenyl-3-pyrazolin-5-one of

glaphenine or N- (7-chloro-4-quinolyl) anthranilic acid 2,3-dihydroxypropyl ester and of

acetylsalicylic acid

these products being well-known analgesics, and,

table X shows the percentages of diminution of the number of painful stretchings observed following the administration of 100 mg/kg/Po of different derivatives.

Moreover, the derivatives of formula I, administered rectally to a rabbit, enabled the pain threshold to be raised in the dentary pulp stimulation test.

As an example, the following table XI gives the results of a comparative study between the activity of derivative code number 730 229 and that of glaphenine, the activities being estimated by the dentary stimulation test

                                      TABLE IX                                     __________________________________________________________________________     Nature of                                                                      tests                105 DE  DE 50  DE 50                                      effected                                                                              Compound tested                                                                              (mg/kg/PO)                                                                             (mg/kg/PO)                                                                            DL 50                                      __________________________________________________________________________                   730 731                                                                               27      >>2 000                                                                               <<1,5.10.sup.-.sup.2                                     730 218                                                                               37      1 500  2,5.10.sup.-.sup.2                                       730 224                                                                               30      >>2 000                                                                               <<1,5.10.sup.-.sup.2                              Compounds                                                                             730 225                                                                               42      >2 000 <2 .10.sup..sup.-2                                according                                                                             730 229                                                                               10      2 800  4.10.sup.-.sup.3                                  to the 730 231                                                                               27      975    3.10.sup.-.sup.2                                  invention of                                                                          730 262                                                                               52      2 500  2.10.sup.-.sup.2                                  Code No.                                                                              730 732                                                                               23      >>2 000                                                                               <<1.10.sup.-.sup.2                         Test with     740 140                                                                               33      >>2 000                                                                               <<1,5.10.sup.-.sup.2                       phenylbenzo   amidopyrine                                                                           45      1 050  4,5.10.sup.-.sup.2                         quinone                                                                               Reference                                                                             glaphenine                                                                            60      1 900  3.10.sup.-.sup.2                                  compounds                                                                             acetylsali-                                                                           72      700    10.sup.-.sup.1                                           cyclic acid                                                             Compounds                                                                      according                                                                             730 229                                                                               45      2 800  1,5.10.sup.-.sup.2                                to the                                                                         invention of                                                            Test with                                                                             Code No.                                                                              730 262                                                                               100     2 500  4.10.sup.-.sup.2                           bradykinine                                                                                  amidopyrine                                                                           48      1 050  5.10.sup.-.sup.2                                  Reference                                                                             glaphenine                                                                            48      1 900  2,5.10.sup.-.sup.2                                Compounds                                                                             acetylsali-                                                                           180     700    2,5.10.sup.-.sup.1                                       cylic acid                                                              Compounds                                                                      according                                                                      to the 730 229                                                                               70      2 800  2,5.10.sup.-.sup.2                                invention of                                                            Test with                                                                             Code No.                                                                acetic acid   amidopyrine                                                                           80      1 050  7,5.10.sup.-.sup.2                                Reference                                                                      compounds                                                                             galphenine                                                                            80      1 900  4.10.sup.-.sup.2                                         acetylsali-                                                                           115     700    1,5.10.sup.-.sup.1                                       cylic acid                                                              Compounds                                                                             730 218                                                                               50      1 500  3,25.10.sup.-.sup.2                               according                                                                             730 225                                                                               80      >>2 000                                                                               <<4.10.sup.-.sup.2                                to the                                                                         invention                                                                             730 229                                                                               23      2 800  8.10.sup.-.sup.2                           Eddy   of Code No.                                                                           730 262                                                                               60      2 500  2,5.10.sup.-.sup.2                         test                                                                                         amidopyrine                                                                           35      1 050  3,25.10.sup.-.sup.2                               Reference     Unactif with                                                     compounds                                                                             glaphenine                                                                            400     1 900                                                           acetylsali-                                                                           >200 (40 %                                                              cylic acid                                                                            with 200)                                                                              700    >2,75.10.sup.-.sup.1                              Compounds                                                                      according                                                                      to the 730 229                                                                               45      2 800  1,5.10.sup.-.sup.2                         Randall                                                                               invention of                                                            and    Code No.                                                                Selitto                                                                        test          amidopyrine                                                                           110     1 050  1.10.sup.-1                                       Reference                                                                      compounds                                                                             glaphenine                                                                            65      1 900  3,25.10.sup.-.sup.2                                      acetylsali-                                                                           110     700    1,5.10.sup.-.sup.1                                       cylic acid                                                       __________________________________________________________________________

                                      TABLE X                                      __________________________________________________________________________                                  Percentage of                                                  Code numero     diminution of                                                  of derivative                                                                          Dose adminis.                                                                          the number of                                     Nature of test effected                                                                     tested  (mg/kg/PO)                                                                             painful stretchings                               __________________________________________________________________________                  730 712 100     60                                                             730 695 100     85                                                             730 136 100     46                                                             730 241 100     67                                                             730 282 100     73                                                Test with phenyl-                                                                           730 283 100     57                                                benzoquinone                                                                                 72 442 100     70                                                              72 462 100     40                                                              72 608 100     55                                                              72 686 130     50                                                              72 701 100     45                                                             730 234 100     55                                                Test with bradykinine                                                                       730 218 100     40                                                Randall and Selitto test                                                                    730 225 100     50                                                __________________________________________________________________________

                                      TABLE XI                                     __________________________________________________________________________                                                 Average                                                                Number of                                                                              increase                                                               rabbits whose                                                                          of pain                                          Dose adm.             pain threshold                                                                         threshold    Duration                            (mg/kg/                                                                               DL 50   Dose adm.                                                                             is increased                                                                           at the peak                                                                            Peak                                                                                of action             Compound tested                                                                              rectally                                                                              (mg/kg/PO)                                                                             DL 50  by 0,5 V                                                                               of activity                                                                            action                                                                              (hours)               __________________________________________________________________________     Compounds                                                                      according                                                                      to the 730 229                                                                               50     2 800   2.10.sup.-.sup.2                                                                      7/10    + 2,9   1 h  2                     invention                                                                      of Code                                                                        Numero                                                                         Compound                                                                              glaphenine                                                                            50     1 900    2,5.10.sup.-.sup.2                                                                   4/10     + 0,63      1                     tested        100    1 900   5.10.sup.-.sup.2                                                                      6/10    + 1,4   45 mn                                                                                1,5                                200    1 900   1.10.sup.-.sup.1                                                                      8/10    + 1,5        2                     __________________________________________________________________________

Tables IX and X clearly show that the compounds of the invention show an analgesic activity superior to that of amidopyrine, glaphenine and acetylsallcylic acid since, to obtain the same effect it is enough to administer them in a dose representing a lesser fraction of the lethal dose.

10. Myorelaxant properties

The derivatives of formula I, preventively administered by oral means to the mouse, reduce the mortality caused by the sub-cutaneous injection of strychnine.

Thus, the derivative of Code No. 72608, administered in a dose of 100 mg/kg/p.o., permits a 50 % protection against the lethality of strychnine.

11. Spasmolytic properties

The derivatives of formula I introduced in the conserving medium, are capable of opposing the contractural action of barium chloride in the isolated duodenum of the rat. This activity is evaluated taking papaverine as standard.

Thus, the derivative of Code No. 730 282 presents a spasmolytic activity double to that of papaverine.

12. Antiinflammatory properties

These properties are shown by a diminution of the local oedema caused by the sub-plantar injection of a phlogogenic agent, such as carraghenine, in the rat following the oral administration of derivatives of formula I.

By way of example, the results obtained by the administration of different derivatives of formula I are listed in the following table XII.

Table XIII, as far as it is concerned, gives the results of a comparative study between the antiinflammatory activity of derivative of Code No. 730 229, on the one hand, and the antiinflammatory activity of amidopyrine, glaphenine and acetylsallicylic acid, on the other hand, these reference compounds being those employed in the comparative study of the analgesic properties.

                  TABLE XII                                                        ______________________________________                                         Code Numero of                                                                             Dose administered                                                                            Percentage reduction                                 derivative tested                                                                          (mg/kg/PO)    of subplantar oedema                                 ______________________________________                                         71 510      100           40                                                   72 255      100           60                                                   72 271      100           35                                                   72 283      100           40                                                   72 311      100           50                                                   72 317      100           35                                                   72 327      100           35                                                   72 419      100           50                                                   72 432      100           45                                                   72 442      100           55                                                   72 462      100           35                                                   72 536      100           35                                                   72 686      25            35                                                   72 773      100           40                                                   72 826      100           60                                                   730 234     100           35                                                   730 243     100           50                                                   ______________________________________                                    

                                      TABLE XIII                                   __________________________________________________________________________                      DE 50  DL 50  DE 50                                           Compound tested  (mg/kg/PO)                                                                            (mg/kg/PO)                                                                            DL 50                                           __________________________________________________________________________     Compound according                                                             to the invention                                                                         730 229                                                                               22     2 800  8.10.sup.-.sup.3                                of Code Numero                                                                           amidopyrine                                                                           140    1 050  1,25..sup.10.sup.-1                             Reference glaphenine                                                                            9      1 900  5.10.sup.-.sup.3                                compounds acetylsali-                                                                           40       700  6.10.sup.-.sup.2                                          cylic acid                                                           __________________________________________________________________________

Table XIII shows that the compound of code numero 730 229 possess a notable antiinflammatory activity, since clearly superior to that of amidopyrine and acetylsalicylic acid, and hardly inferior to that of glaphenine.

As a result of a comparison between the pharmacologically active doses mentioned above, and the lethal doses listed in the following table XIV, the difference between the doses is sufficiently great to permit the utilisation of the derivatives of formula I in therapeutics.

                  TABLE XIV                                                        ______________________________________                                                      Dose administered                                                                             Percentage                                         Code Numero of                                                                              to the mouse   mortality                                          derivative tested                                                                           (mg/kg/PO)     (%)                                                ______________________________________                                         730 732      2 000          0                                                  730 218      1 500          ≃50                                  730 136      2 000          0                                                  730 221        520          ≃50                                  730 224      2 000          0                                                  730 225      2 000          ≃20                                  730 229      2 800          ≃50                                  730 231        975          ≃50                                  730 241      2 000          0                                                  730 379        625          ≃50                                  730 262      2 500          ≃50                                  730 282      1 000          ≃50                                  730 283      1 000          ≃50                                  730 243      1 000          0                                                  730 695      2 000          0                                                  730 712      2 000          0                                                  730 731      2 000          0                                                  730 741      1 500          ≃50                                  740 140      2 000          0                                                  71 510       2 000          0                                                  72 255       2 000          0                                                  72 257       2 000          0                                                  72 260       2 000          0                                                  72 271       2 000          0                                                  72 276       2 000          0                                                  72 283       2 000          0                                                  72 292       2 000          0                                                  72 311       2 000          0                                                  72 317       2 000          0                                                  72 327       2 000          0                                                  72 417       2 000          0                                                  72 419       2 000          0                                                  72 432       2 000          0                                                  72 442       2 000          0                                                  72 450       2 000          0                                                  72 462       2 000          0                                                  72 495       2 000          0                                                  72 502       2 000          0                                                  72 505       2 000          0                                                  72 536       2 000          0                                                  72 613       2 000          0                                                  72 623       2 000          0                                                  72 686       2 000          0                                                  72 687       2 000          0                                                  72 701       2 000          0                                                  72 754       2 000          0                                                  72 778       2 000          0                                                  72 783       2 000          0                                                  72 796       2 000          0                                                  72 826       2 000          0                                                  730 025      2 000          0                                                  72 621       2 000          ≃30                                  72 773       2 000          ≃20                                  72 608       1 600          ≃50                                  730 234      2 400          ≃50                                  ______________________________________                                    

The derivatives of formula (I) are useful in the treatment of gastro-duodenal ulcers, dedemas, anxiety, nervousness, contractions, inflammatory pains and diverse originating pains, cardiac insufficiencies, circulatory insufficiencies, asthma, viscoral spasms and according to the product, hypotension or hypertension.

They may be administered by oral means, in the form of tablets, gelules and dragees, containing 25 to 400 mg of active ingredient (1 to 6 times per day), or suspensions containing 0.2 to 5% of active ingredient (10 to 100 drops, 1 to 3 times per day), by parenteral means in the form of injectable ampoules containing 10 to 15C mg of active ingredient (1 to 3 times per day) and by rectal means in the form of suppositories containing 25 to 300 mg of active ingredient (1 to 3 times per day).

Accordingly the present invention also relates to a therapeutic composition comprising a derivative of the general formula (I) together with a therapeutically acceptable carrier. 

What we claim is:
 1. A compound having the formula ##SPC9##wherein Ar is phenyl or phenyl substituted by a halogen, or a trifluoromethyl, or a methylenedioxy, or one or more methoxy, or an alkyl having one to 4 carbon atoms or a dimethylamino, and wherein R is ##EQU12## wherein n is an integer from 1 to 5, and R₃ and R₄ each is alkyl having one to 3 carbon atoms, or ##EQU13## is morpholino, pyrrolidino, piperidino or hexamethyleneimino.
 2. A compound as claimed in claim 1, in which Ar is phenyl and ##SPC10##
 3. A compound as claimed in claim 1, in which Ar is phenyl and the symbol ##SPC11##is one of the following:4-dimethylaminoethoxyphenyl, 4-di(n-propyl)-aminoethoxyphenyl, 4-pyrrolidinoethoxyphenyl, 4-piperidinoethoxyphenyl, 4-morpholinoethoxyphenyl, 2-morpholinoethoxyphenyl, 3-morpholinoethoxyphenyl, 4-hexamethyleneiminoethoxyphenyl and 4-morpholinopropoxyphenyl.
 4. A compound as claimed in claim 1 in which Ar is 3-chlorophenyl and the symbol ##SPC12##is one of the following:4-dimethylaminoethoxyphenyl, 4-hexamethyleneiminoethoxyphenyl and 4-morpholinoethoxyphenyl.
 5. A compound as claimed in claim 1, in which Ar is a 4-chlorophenyl and the symbol ##SPC13##is one of the following:4-dimethylaminoethoxyphenyl and 4-morpholinoethoxyphenyl.
 6. A compound as claimed in claim 1, in which Ar is 3-fluorophenyl and the symbol ##SPC14##is one of the following:4-dimethylaminoethoxyphenyl, 4-piperidinoethoxyphenyl, and 4-morpholinoethoxyphenyl.
 7. A compound as claimed in claim 1, in which Ar is 3-trifluoromethylphenyl and the symbol ##SPC15##is one of the following:4-dimethylaminoethoxyphenyl, 4-pyrrolidinoethoxyphenyl and 4-morpholinoethoxyphenyl.
 8. A compound as claimed in claim 1, in which Ar is 3,4-methylenedioxyphenyl and the symbol ##SPC16##is4-morpholinoethoxyphenyl.
 9. A compound as claimed in claim 1, in which Ar is 3,4,5-trimethoxyphenyl and the symbol ##SPC17##is one of the following:4-dimethylaminoethoxyphenyl, 4-morpholinoethoxyphenyl, 2-dimethylaminoethoxyphenyl and 2-morpholinoethoxyphenyl.
 10. A compound as claimed in claim 1, in which Ar is 4-methoxyphenyl, 4-methylphenyl or 4-dimethylaminophenyl and the symbol ##SPC18##is 4-morpholinoethoxyphenyl. 